The objectives are to determine the relation of the neuroendocrine system, the aging process, nutrition and reproductive functions to development and growth of mammary and pituitary tumors. (1) Hypothalamic neurotransmitters and related drugs that alter secretion of anterior pituitary hormones will be tested for their effects on mammary and pituitary tumors. The effects of lesions in the raphe (serotonin source) and locus ceruleus (norepinephrine source) also will be tested. (2) Since mammary and pituitary tumors arise primarily in aging rats, and we have found them to be associated with decreased turnover of hypothalamic catecholamines and increased turnover of serotonin, and with increased prolactin and decreased LH-FSH secretion, attempts will be made to prevent these changes by daily treatment with central acting drugs beginning before these changes occur in life. (3) Rats will be underfed or given low protein or high fat diets for only a limited period at the time of carcinogen treatment, or for longer periods after mammary tumor development, to determine their effects on incidence and growth of tumors. Hormones found to be low in the blood as a result of the deficient diets will be administered to determine to what extent they are responsible for reduced tumor incidence and growth. (4) The mechanisms whereby pregnancy and lactation influence onset and growth of mammary tumors will be investigated by measuring pituitary and gonadal hormones in the blood, by studying changes in function of the tumor cells, and by endocrine treatments.